A systematic review of lower extremity arterial revascularization economic analyses

SOCIETY FOR VASCULAR SURGERY® DOCUMENT

A systematic review of lower extremity arterial revascularization economic analyses James P. Moriarty, MSc,a,b Mohammad Hassan Murad, MD, MPH,a,b,c Nilay D. Shah, PhD,a,b Chaithra Prasad, MD,a Victor M. Montori, MD,a,b,d Patricia J. Erwin, MLS,a,e Thomas L. Forbes, MD,f Mark H. Meissner, MD,g and Michael C. Stoner, MDh; on behalf of the Society for Vascular Surgery Committee on Comparative Effectiveness, Rochester, Minn; London, Ontario, Canada; Seattle, Wash; and Greenville, NC Objective: Economic evaluation remains an understudied aspect of lower extremity vascular reconstructions. This study reviewed the economic-based literature with respect to open and endovascular treatment of peripheral arterial disease. Methods: This systematic review included economic analyses of open and endovascular treatment of lower extremity peripheral arterial disease, including claudication and critical limb ischemia. Studies were categorized as model-based, cost-consequences, or econometric cost-analyses. Clinical, financial, and time-based outcomes were examined. Results: From a candidate list of 1351 studies, 19 were appropriate for the review, comprising 3 model-based, 12 cost-consequence, and 4 cost-analyses. Because of the small numbers, claudication and critical limb ischemia studies were analyzed together. There was a trend favoring initial cost-savings with endovascular therapy. Whether this benefit is sustained over time is unknown. We were prevented from drawing cost-efficacy inferences because of a noted lack of standardized patient-centric outcomes, longitudinal data, and reintervention data. Conclusions: The existing lower extremity arterial revascularization economic literature is inadequate for drawing cost-efficacy conclusions and cannot inform guidelines for open vs endovascular treatment. Overcoming this limitation will require the inclusion of cost (initial and reintervention) and patient-centric outcomes in future studies evaluating lower extremity revascularization technologies. All journals, particularly vascular journals, should enforce standard reporting guidelines of effectiveness and economic studies to enable appropriate comparative and cost-effectiveness analyses. ( J Vasc Surg 2011;54:1131-44.)

Technologic advances have resulted in the widespread application of less invasive percutaneous interventions in patients with lower extremity peripheral arterial disease (PAD).1 There are many reported benefits to such an From the Knowledge and Encounter Research Unit,a and the Divisions of Health Care Policy and Research,b Preventive Medicine,c and Endocrinology,d and the Mayo Clinic Library System,e Rochester; the Division of Vascular Surgery, London Health Sciences Centre and the University of Western Ontario, Londonf; the Department of Surgery, University of Washington School of Medicine, Seattleg; and the Department of Cardiovascular Sciences, East Carolina University, Greenville.h The Knowledge and Encounter Research (KER) Unit at Mayo Clinic conducted this work by contract with the Society for Vascular Surgery. Competition of interest: none. Additional material for this article may be found online at www.jvascsurg. org. Reprint requests: Michael C. Stoner, MD, Department of Cardiovascular Sciences, East Carolina University, Greenville, NC 27858 (e-mail: [email protected]). Independent peer-review and oversight has been provided by members of the SVS Document Oversight Committee (K. Wayne Johnston, MD (chair), Enrico Ascher, MD, Jack L. Cronenwett, MD, R. Clement Darling, MD, Lois A. Killewich, MD, PhD, Thomas F. Lindsay, MD, John J. Ricotta, MD). 0741-5214/$36.00 Copyright © 2011 Published by Elsevier Inc. on behalf of the Society for Vascular Surgery. doi:10.1016/j.jvs.2011.04.058

approach compared with the traditional strategy of bypass surgery, including reductions in periprocedural morbidity and mortality. However, concerns remain regarding clinically important patient benefits, long-term durability, and rates of reintervention associated with percutaneous treatment strategies. The rapid proliferation of new technologies has left the vascular specialist with an array of potential therapies to treat PAD, often without rigorous outcome data or cost-efficacy information to guide responsible treatment decisions. These issues have gained special relevance since the Patient Protection and Affordable Care Act was signed into law in 2010 in concert with the implementation of other initiatives to “bend the curve” of rising health care costs. In this context, comparative effectiveness research (CER) has received increased attention. The United States Congress has appropriated ⬎$1 billion to support this national initiative, while asking the Institute of Medicine to identify priority topics. Lower extremity PAD has been identified as one of these priorities.2 The Society for Vascular Surgery (SVS) strongly endorses the use of CER to completely evaluate the available options for the treatment of PAD.3 The purpose of the present report is to review and describe the 1131

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current literature regarding economic evaluations of endovascular and open treatment alternatives in patients with lower extremity PAD. METHODS A systematic review was conducted following a protocol established a priori and according to the recommendations of the Cochrane Collaboration and reported using the relevant items from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).4,5 Eligibility criteria. Eligible studies were (1) original comparative studies that (2) included an economic or cost analysis of (3) endovascular vs surgical interventions for revascularization in patients with PAD presenting with intermittent claudication and critical limb ischemia (CLI). We included studies regardless of size, date of publication, follow-up length, language, or design. The eligibility criteria were inclusive of nonatherosclerotic disease processes, although the final selection of economic and cost articles included only atherosclerotic disease patients. Literature search. The initial search strategy was developed on Ovid MEDLINE (1950-September 2009) and applied to the databases as noted in the Appendix (online only) using a combination of medical subject headings (MeSH), subheadings, and text words. The subject headings peripheral vascular diseases (expanded to include all related terms), arterial occlusive diseases, arteriosclerosis or thromboangiitis obliterans, and intermittent claudication were augmented with textwords such as “peripheral angiopathy,” PVD or PAD or PAOD, leg or limb ischemias, critical or threatening limb or leg injury, as well as specific vascular terms (eg, inguinal, saphenous, femoropopliteal). The economics concept also used a combination of subject headings economics/or cost and cost analysis/subheadings (economics attached to various procedures), and textwords such as cost, reimbursement, saving, money, dollar, and “cost-effective.” The final concept was the treatments of interest, physical therapy modalities, vascular surgical procedures, and angioplasty techniques. The detailed strategies are available in the Appendix (online only). We also reviewed references of included studies and contacted experts on comparative effectiveness from the SVS to obtain additional references. The references from the experts were used to benchmark the search strategy’s comprehensiveness. Study selection and data extraction. Two reviewers working independently reviewed all abstract and titles, and potentially eligible studies were selected for full-text assessment. The abstract reviewers erred on the side of inclusion, and all disagreements at this stage were included for evaluation of the full-text report. Reviewer pairs had adequate chance-adjusted inter-reviewer agreement in assessing the eligibility of full text articles using the inclusion and exclusion criteria described above (␬ statistic ⫽ 0.72). Disagreements at the full-text stage were resolved by consensus or arbitration. Data extraction was always confirmed by a second reviewer. Our data collection approach followed the sug-

gestions made by Pignone et al.6 We extracted data describing patient demographics, surgical procedures, study design (randomized controlled trial, observational, model-based, other), clinical outcome unit (qualityadjusted life-years [QALY], life-years, etc), cost measurement and perspective (charges, payer cost, provider cost, societal cost), and adjustment methods (future cost discount, retro-inflation, inflation year). Analysis. Although a meta-analysis of cost-effectiveness studies would have been desirable to estimate pooled costeffectiveness ratios, these studies were scant, and their results were inconsistent in methods and findings, which limited the value of pooled estimates. Thus, the analyses presented in this report focus on describing the results of the included studies across the three categories suggested by Drummond et al7 (Table I). RESULTS Search results. The literature search, supplemented by references provided by content experts from the SVS, yielded 1351 references. After title and abstract screening, 92 references were deemed eligible and were retrieved for full-text screening. Of these, 19 met criteria to be included in the analysis.8-26 A detailed schematic of the search results is depicted in the Fig. The number of suitable studies was relatively scant, and as a result, claudication and CLI studies were considered together in an attempt to identify significant trends and patterns in the literature. Study type and quality. Table II presents a summary of the included studies by study type (model-based decision analysis, econometric cost-analysis, or a cost-consequence analysis). Table III describes all included studies. Of the 19 studies, 12 were cost-consequence studies reporting at least one clinical outcome as well as an economic outcome, 11 compared open surgery with endovascular treatment, and the remaining 7 included additional treatment approaches. The most common perspective (14 studies) was of the health care provider, which only looks at direct costs to the heath care institution. The remaining four studies used a societal perspective, which includes all costs to society regardless of who actually incurs them. All but one study used patient-level direct costs in the analysis. Nine studies did not use any type of sensitivity analysis. Model-based studies used the most robust approaches to sensitivity analyses. All other studies that performed sensitivity analyses primarily did so by using subgroup analyses or by including different types of costs. Nine studies gave no details or offered incomplete information about the approach to adjust for inflation and discounting. Model-based studies. Model-based studies include all those that pool retrospective data and use statistical methods to derive outcomes. The modeling studies were the most homogeneous in study design,11,13,19 offered the longest time horizon (5 years in 1 and lifetime horizon in 2 studies), used QALY as the clinical outcome, and used equivalent clinical and economic outcome time horizons within each study. All these studies found no dominant or dominated treatment strategy. Furthermore, two of the

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Table I. Summary of analysis types, with pros and cons Analysis type

Description

Model based

An analytic representation of the problem at hand that uses previously reported data as model inputs

Econometric cost analysis

An appraisal that uses quantitative and statistical methods to analyze economic outcomes only and not clinical outcomes together An appraisal that reports both economic and at least one clinical outcome together

Cost consequences

Pros ● Analytic flexibility ● Less costly/time-consuming than clinical trials ● All available information can be synthesized together ● All uncertainty in model inputs can be taken into account simultaneously ● Simple to perform ● Easily understandable

● Reporting both economic and clinical outcomes allows for the ability to represent potential trade-offs of changing from standard of care to a new approach

Cons

● Does not allow for a complete picture needed for informed decision making ● Trade-offs may be abstract and difficult to judge “a good trade”

Fig. Schematic of search results and study selection.

three studies found that the optimal strategy in the incremental cost– effectiveness ratio was sensitive to indication.13,19 In these studies, catheter-based therapy was more cost-effective or provided greater net health benefits in patients with claudication, whereas initial bypass was most cost-effective or provided the greatest limb salvage benefits in patients with CLI. The inconsistency in results across these studies suggests that the optimal strategy, in both patient benefits and costs, may depend on patient characteristics, lesion anatomy, degree of ischemia, procedural technique, and perioperative care, the latter 2 of 10 related to learning curves, teamwork, and procedural volume. However, these features were not sufficiently described in the study reports. Cost-analyses studies. These studies only focus on economic outcomes. Two of the four cost-analyses studies compared endovascular techniques with open surgery, whereas the other two included amputation as a third comparator.10,15,20,24 Only one study20 used a societal

perspective. This study was also unique in that the authors used macro-level cost data for the analysis, estimating the costs at a national level and then imputing costs per patient. The main outcome of the cost analyses was consistent across all studies and showed the endovascular approach was the least costly in the short-term. Cost-consequence studies. Although there were some similarities, the studies conducting a cost-consequence analysis were heterogeneous in their measurement of costs and outcomes.5,8,9,12,14,16-18,21-23,25,26 Five studies focused on patency, amputation-free survival, or overall mortality. QALY was the only outcome in one study. Patency, length of stay, and death were the outcomes in the other six studies. Six of the 12 studies had a time horizon for the clinical outcome of ⱕ1 year (including surgical episodes only). Five of the remaining studies used a time horizon between 1 and 5 years. Conversely, only three studies had a time horizon for cost data ⬎1 year. Five studies only assessed the costs of the surgical episode. The time horizon was consistent between clinical

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Table II. Summary of included studies group by analysis type Measurement Type of study

Treatment comparisons 11,13,19

Model based: 3 studies

ET and surgery only: 1

Outcomes QALY: 3

Costs Secondary data sources: 3

ET, surgery, and other(s): 2 Cost analysis: 4 studies10,15,20,24

ET and surgery only: 2

None: 4

ET, surgery, and amputation: 2 Cost consequences: 12 studies5,8,9,12,14,16-18,21-23,25,26

ET and surgery only: 10 ET, surgery, and other(s): 2

Time horizon

Patient level: 3

Outcomes Lifetime: 2

Lifetime: 2

5-10 yrs: 1

5-10 years: 1

NA

Surgical episode only: 2 1-5 years: 1

Macro level: 1 Patency: 2

Patient level: 12

Costs

ⱕ1 yr: 4

QALY: 1

1-5 yrs: 5

LOS: 2 Mortality: 2

5-10 yrs: 1 Surgical episode only: 2

5-10 years: 1 ⱕ1 year: 4 Surgical episode only: 5 1-5 years: 3

Multiple: 5a ET, Endovascular treatment; ICER, incremental cost-effectiveness ratio; LOS, length of stay; NA, not applicable; QALY, quality adjusted life-year. a Patency/amputation-free survival/mortality.

outcomes and costs in 7 of the 12 studies, and the remaining 5 measured costs in a shorter time horizon than the clinical outcomes. For clinical outcomes, three studies favored surgery and seven favored endovascular revascularization, whereas two other studies did not report outcomes separately for the two procedures. All studies used patient-level direct data, presented the results from the health care provider perspective, and found the endovascular approach was the least costly. Closer inspection of these studies suggests that only three offered results of importance, insofar as they assessed patient important outcomes (quality-adjusted time without symptoms of disease or toxicity of treatment, QALY, years of leg saved, and death) and considered cost and outcome horizons of ⬎1 year.14,17,23 These three studies, of which only one considered a time horizon of 5 years, suggest similar clinical outcomes across procedures but lower costs with endovascular approaches. DISCUSSION Main findings. Although this review provides insight into the current status of economic evaluations of the invasive treatments of PAD, the limitations of the data provide few meaningful conclusions about the economic ramifications and, more importantly, the costeffectiveness of different treatment options. Endovascular therapy appears to be the least costly option in the short-term; however, the long-term clinical and economic consequences of these procedures remain unclear. The current cost-effectiveness data in the literature are relatively coarse (indication dichotomized between CLI and claudication) and tend to lack anatomic information, detailed patient information, functional status, and

patient-centric outcomes. A cost-conscious evidencebased decision regarding a patient’s optimal treatment strategy depends on these factors, which are clearly lacking from the exhaustive review presented in this report. Implications for policy and research. As opposed to what we found in many of the studies included in this review, economic evaluation studies should pay attention to indication, anatomy, patient comorbid and functional profile, choice of patient-important outcomes, and use of comparable time horizons for both cost and clinical outcomes. The available options vary by indication. Studies evaluating patients with intermittent claudication should consider endovascular interventions, bypass surgery, as well as medical and exercise therapy. Studies evaluating patients with CLI will have to consider also primary amputation as an option. Surrogate markers, such as patency and procedural times, which are important perhaps in evaluating the technical feasibility of a procedure, at best indirectly inform the extent to which these procedures offer benefits that patients value. These studies should focus instead on patient-important outcomes such as health-related quality of life and functional capacity (eg, walking distance) in patients with intermittent claudication; and limb salvage, death, and freedom from major adverse limb events in CLI,27 as well as periprocedural events that patients value avoiding, including severe bleeding, limb loss, cardiovascular events, and death. Complete economic evaluations should use comparable time horizons for both cost and clinical outcomes to appropriately compare their relationship. Because of these limitations, this review cannot offer clear and strong infer-

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Table II. Continued. Outcome and cost horizons equivalent

Cost perspective

Yes: 3

Societal: 1

Surgery preferred: 1

No treatment preferred: 1

Health care provider: 2

Dependent on patient characteristics: 2

Dependent on patient characteristics: 2

NA

Societal: 1 Health care provider: 3

None: 4

ET preferred: 4

Yes: 7

Societal: 2

Surgery preferred: 3

ET preferred: 12

No (cost timeline shorter): 5

Health care provider: 10

ET preferred: 7

Outcome results

Cost results

ICER results Drug therapy, followed by no treatment preferred: 1 Dependent on patient characteristics: 1 PTA: 1 NA

Dominant or dominated strategies Dominant strategies: 0 Dominated strategies: 0 NA

ET dominant: 7

Indeterminable: 2

ences about the relative cost-effectiveness of the treatment options of interest, a common finding in systematic reviews of economic analyses.28 The four cost analyses allow us to observe that a therapeutic innovation, such as an endovascular procedure that reduces the need for hospitalization, also reduces direct patient costs around the time of the index procedure. However, these are partial economic analyses because no assessment of patient outcomes took place. Furthermore, it is difficult to draw definitive conclusions regarding cost differences given the differences in time horizons across these four studies. Also, two of the studies only reported costs of the surgical episode, potentially missing any costs due to reintervention. The cost-consequence studies could overcome some of the limitations we just discussed. However, only 4 of the 12 studies included patient-important outcomes, such as quality of life and amputation-free survival.8,17,23,25 Furthermore, the inclusion of both costs and clinical outcomes requires equivalent time horizons for both of these elements. When the time horizon for outcomes is longer than the horizon for costs, which results from difficulties capturing long-term costs, costs associated with long-term management and reintervention may be missed, particularly when the initial treatment had limited durability. Only 9 of the 19 studies reported conducting sensitivity analyses, the type of which varied importantly.9,11-13,17-20,22 These included subgroup analyses based on patient characteristics and clinical outcomes, one-way and multiway sensitivity analyses of model parameters, and the exclusion of certain costs such as professional fees and those not occurring during the surgical procedure. In general, sensitivity

analyses had no effect or showed results that favored endovascular treatment. Model-based studies enable analysts to consider many levels of uncertainty (Table I). The assumptions of the three model-based studies are not identical, but they are fairly similar. None suggest a dominant endovascular or open surgical strategy that is appropriate for all patients. The two studies that used the health care provider perspective had similar conclusions, although through different assumptions.13,19 Both studies found endovascular treatment was optimal or cost-effective for most patient indications and lesion types; bypass surgery was optimal for patients with rest pain or tissue loss and for those presenting with occlusion, regardless of graft type. However, the study by Hunink et al13 found an endoluminal strategy was optimal for certain patients with stenosis. This strategy was not included in the Muradin et al19 study. The final modelbased study found that drug therapy, a treatment approach unique to this study, had the lowest cost per QALY.11 However, this study also found that all approaches were cost-effective with the baseline comparator approach of no treatment. Future work reporting economic analyses would benefit greatly from following guidelines recommended by the International Society of Pharmacoeconomics Outcomes and Research.29,30 Specifically, research performing sensitivity analyses with varying time horizons could help identify interactions between cost-effectiveness and time. If this were the case, treatment by patient and anatomic characteristics could be tailored more appropriately. However, subgroup analyses are seldom reliable, and systematic skepticism should be exercised.31 Such research should optimally focus on patient-important outcomes such as disease-

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Table III. Description of included studies First author (year) Model-based Hunink13 (1995)

Patients (n; age) procedures Study design Cost analysis methods

Outcome

Cost perspective

Adjustment method

Outcomes

Fem-pop disease Markov amenable to model PTA or BS, (NR, ⱖ65)

A two-staged treatment QALY approach is used based on the PTA, bypass, or no treatment. Strategies include no treatment; no treatment, PTA; no treatment, PTA-PTA PTA-bypass, bypass; no treatment, and bypass-bypass. Cycle time not explicitly given but appears to be 1 year long.

Health care provider

1990 US$

QALYs based on values of health states derived from the Torrance Multi-Attribute Scale.

Muradin19 (2001)

Fem-pop arterial Markov disease. Base model case (NR, 65yo man). Bypass vs PTA vs hypothetical ET

PTA vs BS vs hypothetical ET device. Assumed willingness to pay for 1 QALY $20,000.

Health care provider: costs

1999 US$

Health state QALYs were estimated using an abbreviated form of the Health Utilities Index.

Holler11 (2006)

Drug therapy, Markov ET, BS, or model NT (NR, 65)

A two-staged QALY treatment approach based on the 4 options resulting in 16 differing treatment strategies. 1-year Markov cycles.

Societal

2001, 5% Life expectancy discount and QALYs rate generated for all treatment options.

ET (35; age 71) RCT vs BS (38; age 71)

DUCC

None, cost analysis only

Health care provider

1994 Dutch None given guilder, converted to US$

BS (96, age NR), ET (111, age NR); or amputation (114, age NR)

DUCC, also None, cost segmented between analysis cost categories only

Health care provider

1996

Cost analysis van Dijk24 (1997)

Eneroth10 (1996)

O–R

QALY

Hospital days are not given by surgical group, little to go on.

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Table III. Continued. Time horizon

Costs included

Cost unit

Sensitivity analysis

Life-time costs, simulated until entire cohort had died

Hospital and One-way sensitivity US$ physician costs analyses and multiway for initial and sensitivity analysis secondary (simultaneous change procedures, followin all treatment up, amputation variables to a and rehabilitation, favorable direction). and long-term care Sensitivity analyses based on $50,000 per QALY threshold.

Life-time costs, simulated until entire cohort had died

Treatment cost One-way sensitivity US$ related to disease using age, sex, (initial/subsequent willingness to pay, procedures, tests discount rate, risk of for follow-up, hypothetical device routine (morbidity mortality, examinations, time lost). Age, sex, amputation and willingness to pay, rehabilitation, and device risk used annual costs of in 4-way sensitivity amputation or analysis. major morbidity).

5 years, both outcomes and costs

Direct and indirect One-way sensitivities costs from a of ⫾ 10% of societal perspective transition by health state probabilities. based on survey data. No more details given beyond this.

Short-term, surgical episode only

Direct costs from None hospital episode; operation costs, postop care, treatment of AVfistulae 6 years or Direct patient costs None until death from hospital (details on episode, postsurgical rehabilitation clinic episode and nursing home costs very costs vague)

€

Outcomes

Cost results

ICER

Results based on Results based For patients with stenosis indication and on indication or with an occlusion stenosis/ and stenosis/ and disabling occlusion; occlusion; claudication: initial overall figures overall figures PTA increased not given. not given. effectiveness and saved lifetime expenditures vs BS, PTA; PTA always dominant vs NT; PTA-BS increased effectiveness further for some, most ICERs ⬍$50,000 per QALY gained. In patients with an occlusion and chronic critical ischemia: initial BS yielded the highest effectiveness and was cost-saving or cost ⬍$2000 per QALY gained vs NT. BS highest NHB PTA costs range Reported as net health for patients $22,758benefits with assumed with chronic $65,578 society willingness to critical depending on pay. PTA had higher ischemia and indication; net health benefits than occlusion, bypass cost bypass in most, but not PTA highest range all indications. NHB in $33,229stenotic fem$53,346 pop lesions. depending on Highest indication. QALYs achieved by PTA. BS/BS option BS/BS most Lowest ICER ($2321.21) most effective costly is achieved with the (1.838 (10,420.10 drug therapy/NT QALY); NT/ average total strategy; highest ICER NT least costs); NT/ ($12,522.50) is effective NT least achieved with the NT/ (0.802 costly BS. NT/PTA, drug QALY) (5941.80 therapy/PTA, PTA/ average total PTA, BS/PTA, drug costs) therapy/BS, PTA/BS all dominated by another strategy having the same first-line treatment.

US$

None

ET, $6322; BS, No clinical outcomes, $8030 cannot be calculated

US$

None

BS, $46,000; No clinical outcomes, ET, $41,000; cannot be calculated amputation, $54,000

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Table III. Description of included studies First author (year)

Patients (n; age) procedures Study design Cost analysis methods

Outcome

Cost perspective

Adjustment method

Myhre20 (1998)

BS (46; age 72) O–R vs amputation (44; age 75) vs PTA (extrapolated data)

DUCC, costs reported None, cost on an annual basis, analysis only by procedure and national estimates.

Societal

Jansen (1998)15

Occlusive PVD, O–P (age 65.6). BS (487) vs PTA (96)

Multiple linear regression analysis, DUCC

Health care 1995 US$ provider ⫺ costs

None, cost analysis only

1996 US$

Outcomes None given

NR. LOS used as an explanatory variable. One table gives LOS for certain groups of patients but does not match previous grouping.

Cost consequences Stoner22 BS (183; age O–R (2008) 63.9) ET (198; age 66.0) Adam (2005)8 ET (224, ⬍70: RCT 30%, 70-79: 46%, ⱖ80: 24%) BS (228: ⬍70: 35%, 70-79 39%, ⱖ80 26%) Whatling26 BS (87; age O–P (2000) 67.9), ET (51; age 61.9)

Amortized cost model Patency Health care to calculate cost per provider day of patency at any given time. Unadjusted inpatient Amputation-free Health care costs per day survival, allprovider cause mortality, utility (EuroQuol 5D and SF36

Patency is compared using KM curves. Inflated to Morbidity, FY 2003additional 04 treatments, KM survival curves, HRQL

DUCC

Patency

Health care provider

NR

Patency is compared using KM curves.

DUCC, median costs reported

Mortality

Societal

NR

1-year mortality percentage reported by group.

LOS

Health care provider

1984 costing year

Mean LOS, descriptive only, no statistical test performed.

Singh21 (1996)

BS (52), ET (52), amputation (46; overall age 71

O–P

Jeans16 (1986)

BS (13), ET (11)

Not specific DUCC on a subset of but patients appears to be O–R

NR

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Table III. Continued. Time horizon

Costs included

Sensitivity analysis

Cost unit

Outcomes

Cost results

ICER

1 year

Procedure costs, Different medical treatment, reimbursement and nursing home approaches used for stays sensitivity analysis.

US$

None

Short-term, surgical episode only

All costs of surgical episode except physician fees

US$

None

12 months

Initial surgical Subgroup analyses US$ ET patency, BS, $12,389; Open surgery: $229/day episode (direct and based on clinical data 78%; BS, 66% ET, $6739 of patency; ET: $185/ indirect), adverse and outcomes. day of patency events postsurgery Inpatient hospital None British £ BS 1-year BS, 23,322; ET, NR. ET would direct costs amputation17,419 dominate. free survival: 68%; ET 1year amputationfree survival: 71%

12 months, both costs and outcomes. High rates lost to follow-up ⬎12 months.

None

Outcomes up Inpatient hospital None to 6 years, direct costs short-term for costs (intervention only) 1 year, both Direct patient costs None mortality of initial and costs hospitalization, selected follow-up costs, some patient out-of-pocket costs

Short-term, surgical episode only

Direct patient costs

None

BS $6971 per No clinical outcomes, patient, $5.23 cannot be calculated million nationally; amputation $21,200 per patient, $16.77 million nationally, PTA $1855 per patient, $740,000 nationally Weighted costs No clinical outcomes, calculate to cannot be calculated BS, $19,008; PTA, $10,356

British £ BS patency: 99%; BS, 3072; ET, ET patency: 1912 68% (at 6 years)

NR. A break-even point of percentage of ET failing (48%) is calculated.

British £ ET: 25.0% ET, 5443; BS, mortality; BS: 6766; 23.1% unilateral mortality; amputation, unilateral 10,162; amputation: bilateral 32.4% amputation, mortality; 13,848 bilateral amputation: 33.3% mortality. British £ Greater LOS for Surgical, 1328; BS patients dilatation, (13.7 vs 2.8) 301

NR. No difference in clinical outcomes, simplifies to a cost minimization analysis.

NR. ET would dominate.

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Table III. Description of included studies First author (year)

Patients (n; age) procedures Study design Cost analysis methods

Sultan (2009)23

PTA (190; age O–P 73), BS (119; age 70)

Laurila (2000)17

PTA (86; age O–P 70.3) or BS (38; age 73.7)

Hunink12 (1994)

Fem-pop PTA O–P (71; age 64.6) vs BS (228; age 66.4)

Mertens18 (2005)

DUCC, total group costs reported, average costs reported based on procedure number (includes repeats) DUCC

Outcome Q-TWiST, QALY

Cost perspective Health care provider

Adjustment method NR

Outcomes QOL analysis uses Q-TWiST to calculate QALYs.

Reoperation-free Health care years and year provider of leg saved

Converted KM curves for from patency rates, Finnish reoperationmarks to free cases, and US$, year leg salvage not rates explicitly given, appears to be 1994

Multiple linear regression analyses using stepwise selection

LOS

1990 US$

Infrarenal O–R arterial stenoses (n, age NR). 442 episodes for 343 patients: surgical 221, ET 199, mixed 22)

DUCC

Mortality, LOS Societal

Ballard9 (1998)

Severe aortoiliac O–R occlusive disease. ET (65; age 67), BS (54; age 64)

DUCC, Student t test Survival and performed. primary patency

J. d’Othée14 (2008)

Intermittent O–R claudication due to aortoiliac and/or fempop disease. ET (64; age 62.7), BS (33; age 63.6)

Univariate and Primary Health care NR multivariate analysis outcome is provider ⫺ (log transformation) cost. Multiple direct and using direct and clinical indirect indirect costs from a outcomes, costs from cost accounting including a cost system, descriptive patency and accounting unadjusted as well. mortality system

Health care provider

Health care provider

NR

NR

LOS only outcome used. Same analysis used as for costs. Wald test used for significance. KM curves for survival, descriptive comparison for LOS, multivariate regression performed on amputationfree and reinterventionfree survival. KM curves for survival and primary patency. No significant difference in survival.

P values only listed for those that are significant (NS for all others). KM curve given for follow-up duration.

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Table III. Continued. Time horizon

Costs included

Cost unit

Sensitivity analysis €

5 years, both outcomes and costs

Direct patient cost of None inpatient events only, includes initial treatment.

3 years, both outcomes and costs

Hospital costs, including initial operation and 3year follow-up. Specific costs include hospital stay, ICU stay, radiologic exams, and operations.

Short-term, surgical episode only

Costs for primary Subgroup: patients with US$ episode. Physician 1 admission during fees were excluded. the study time period

Subgroup analyses US$ based on occlusion length (under 10 cm and under 15 cm).

Outcomes

Cost results

ICER

QALY– PTA, 2.058; BS, 2.042

PTA, 12,637; BS, 20,142 (manually calculated)

NR. PTA would dominate.

3-year patency: PTA $8855; Cost per reoperation-free BS 52%, PTA surgery year: PTA $4466; 45%; 3-year $16,470 surgery $7418. Cost reoperationper leg saved: PTA free cases: BS $3877; surgery $6055. 68%, PTA 56%, 3-year leg salvage rate: BS 90%, PTA 79%. No significant differences found in any outcome measure BS resulted in an BS resulted in NR. Adjusted ICER (adjusted) an (adjusted) $799.68 per hospital increase in increase in day (BS dominated). LOS of 6.3 costs of days (P ⫽ $5038 (P ⫽ .0004) .006)

Outcomes up “Total health Subgroup analysis of € to 5 years insurance costs”: selected anatomic site after physician fees for of procedure procedure, main procedure, cost analysis charges for hospital 30 days stay, ET devices or before grafts, drugs, intervention anesthesia, x-rays, to 6 weeks laboratory tests, after other fees/costs

95% of patients ⬍70 years survived ⱖ4 years, 70-79 had ⬍80% survive ⱖ4 years, half of the patients ⱖ80 years died ⱕ6 months.

Up to 46 months for outcomes (mean, 22 months), costs are short-term (hospital episode only)

ET survival Mean hospital NR. Time periods not ⬃97% by 24 costs, consistent. Raw data months, BS including for main outcome survival ⬃90% professional variable (survival) not by 24 months. fees: ET reported. Significant $9161; BS improvement $10,585. No of primary difference patency for BS statistically, vs ET at 18 including months (P ⫽ sensitivity .002). analyses. 1-year patency: Total costs: ET NR ET 94%; $11,849; BS surgery 95%. $15,577. “Late” Multivariate mortality: ET analysis found 9.4%; BS ET approach 15.2% had 25% reduction in costs, all else equal.

Costs for surgical episode

Re-ran analyses excluding professional fees and for only direct procedure costs

Not specific. Initial surgical None Mean episode (direct and follow-up– indirect), ET, 941 outpatient and days; inpatient costs surgical, during follow-up 1138 days. Cost and outcome time frame appear to be the same.

US$

US$

Surgical: $4437; NR. Only can be done ET by using cost per median surgeon: LOS for BS ($369.75), $3643; ET by ET by surgeon radiologist: ($910.75), ET by $2358 radiologist ($2358).

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1142 Moriarty et al

Table III. Description of included studies First author (year)

Patients (n; age) procedures Study design

Werneck25 (2009)

CLI, high O–R operative risk (age 69). BS (32) vs PTA (45; only 26 used for cost analysis)

Cost analysis methods

Outcome

Cost perspective

Adjustment method

DUCC, nonparametric Amputation-free Health care NR Mann-Whitney U survival and provider ⫺ test. overall survival costs (only appears to be for PTA patient)

Outcomes KM curves but only for overall survival.

BS, Bypass surgery; CLI, critical limb ischemia; DUCC, descriptive unadjusted cost comparison; ET, endovascular treatment; FY, fiscal year; HRQL, health-related quality of life; ICER, incremental cost-effectiveness ratio; ICU, intensive care unit; KM, Kaplan-Meyer; LOS, length of stay; NHB, net health benefit; NR, not recorded; NT, no treatment; O–P, observational prospective; O–R, observational retrospective; PTA, percutaneous transluminal angioplasty; PVD, peripheral vascular disease; QALY, quality-adjusted life-year; QOL, quality of life; Q-TWiST, quality-adjusted time without symptoms of disease or toxicity of treatment; RCT, randomized controlled trial; SF36, Short Form 36-item survey; US$, United States $.

specific and overall quality of life, functional ambulatory measures in claudication, and major adverse limb event-free survival in CLI. Strengths and limitations. Because of the relatively small data set to work with, we were obliged to accept several notable limitations with respect to inclusion criteria: First, we included series that examined nonatherosclerotic disease processes. Still, almost all of the studies presented represent atherosclerosis patient populations. Second, we did not separate claudication from CLI. Again, this compromise was made because of the small numbers and lack of separation seen in many of the economic studies examined. We acknowledge that these are a heterogeneous group of studies, with different treatment indications and outcome measures, such as patency, limb salvage, and functional status. This glaring issue should be addressed in future studies through adherence to reporting standards and provision of accepted objective measures of limb ischemia. This review has several other notable limitations. Nine of the 19 eligible studies were published ⬎10 years ago, the oldest was published 23 years ago, and modeling studies also had to rely on older data. Outdated evidence threatens the applicability of our findings. Unfortunately, the scarcity of studies precluded performing a sensitivity analysis based on data “vintage.” Lack of data precluded economic analyses of reinterventions. The inclusion of both claudication and CLI studies, because of the scant literature, introduced inconsistency into the review. Publication bias and inconsistency across studies also threaten the validity of the conclusions of this report. Inconsistency in approach, model assumptions, choice of options, outcomes of interest, and source and quality of data for clinical and cost outcomes, and actual variation in cost structure (ie, hospital costs, professional fees,

reimbursement rates and other determinants of cost vary across health systems and countries) limit the comparability of and the ability to meta-analyze the available data. Finally, the review was commissioned by the Society for Vascular Surgery and several of its members were authors of this report. A rigorous protocol of review to which we adhered sought to limit the introduction of points of view that may have favored one or the other intervention. The strengths of this report stem from the comprehensive literature search, a priori established protocol and inclusion criteria, and bias protection measures undertaken during the conduct of this review, including selection of evidence by pairs of nonconflicted reviewers working independently. CONCLUSIONS We found only very low quality evidence (ie, studies with major methodologic limitations, including inconsistent and brief time horizons, narrow selection of treatment options and outcome measures, poorly reported, scant, potentially outdated, and inconsistent in their methods and results) providing economic inferences about the relative merits of endovascular and open surgical approaches to the treatment of PAD patients. Therefore, any inferences are weak and are likely to change with new research. Although endovascular procedures appear less costly in the short-term, long-term comparison between catheter-based procedures and open revascularization in cost and patient-centric outcome remains uncertain. In addition, more data need to be analyzed to assess the role of effective nonoperative therapies (eg, drugs, exercise) that may produce clinical benefit at lower costs and may

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Moriarty et al 1143

Table III. Continued. Time horizon

Costs included

Cost unit

Sensitivity analysis

Mean follow- Direct hospital costs None up for of surgical episode. outcomes was 7.7 months, time horizon for primary end point unknown, costs are only shortterm for primary surgery.

Outcomes

US$

represent more cost-effective alternatives than anatomic treatments. Additional research is needed to investigate the uncertainties of cost-effectiveness of PAD treatment. Such research should optimally focus on patient-important outcomes such as disease-specific and overall quality of life, functional ambulatory measures in claudication, and major adverse limb event-free survival in CLI. The current state of the data and literature underscore the importance of professional society-backed database efforts and mandate that cost and durability be accounted for as new technologies are assessed. Furthermore, vascular journal editorial boards should mandate that all reports follow standard reporting guidelines to allow for appropriate comparative economic analyses.

ICER

75.5% PTA $2910.60; NR, no outcomes for BS amputationBS apparent to do an free survival $17,703.50 ICER for PTA, 80% overall survival at 15 months.

9.

10.

11.

12.

13.

14.

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Additional material for this article may be found online at www.jvascsurg.org.

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Appendix: (online only). Search strategy MEDLINE (1950-2009) October week 4 EMBASE (1988-2009) week 45 Adj ⫽ adjacent terms (adj3 ⫽ within 3 words) Exp ⫽ explode, expand to include all terms in subhierarchy /ec ⫽ subheading economics /subject heading, either MeSH or EMTREE .fs. ⫽ floating subject heading (applied anywhere in subject headings) .mp. ⫽ title, original title, abstract, name of substance word, subject heading word, unique identifier *or $wild card truncation 1. exp Peripheral Vascular Diseases/ec [Economics] 2. arterial occlusive diseases/or arteriosclerosis/or exp thromboangiitis obliterans/ 3. arterial occlusive diseases/ec or arteriosclerosis/ec or exp thromboangiitis obliterans/ec 4. 1 or 3 5. 4 and su.fs. 6. vascular surgical procedures/ec or angioplasty/ec or blood vessel prosthesis implantation/ec or stents/ec or “tissue and organ harvesting/ec”.mp. [mp⫽title, original title, abstract, name of substance word, subject heading word, unique identifier] 7. exp physical therapy modalities/ec or amputation/ec or occupational therapy/ec 8. angioplasty, balloon/ec 9. exp “costs and cost analysis”/or exp economics, hospital/or exp economics, medical/or exp “fees and charges”/ 10. length of stay/or hospital costs/or models, economic/or postoperative complications/ec 11. life expectancy/or absenteeism/or http://employment.mp. or http://unemploy*.mp. or recovery of function/or return to work/[mp ⫽ title, original title, abstract, name of substance word, subject heading word, unique identifier].11. life expectancy/or absenteeism/or employment.mp. or unemploy*.mp. or recovery of function/or return to work/[mp⫽title, original title, abstract, name of substance word, subject heading word, unique identifier] 12. Quality-Adjusted Life Years/ 13. (pvd or pad or paod).mp. or peripheral vascular disease/or intermittent claudication/or claudicat*.mp . or ischemia/or ischaem* [mp⫽title, original title, abstract, name of substance word, subject heading word, unique identifier] 14. ((peripheral or femoropopliteal) adj3 angiopath*).mp . [mp⫽title, original title, abstract, name of substance word, subject heading word, unique identifier] 15. ((leg or limb) adj2 (ischemi* or ischaemi*)).mp . [mp⫽title, original title, abstract, name of substance word, subject heading word, unique identifier] 16. ((critical* or threaten*) adj3 (limb* or leg*)).mp . [mp⫽title, original title, abstract, name of substance

Moriarty et al 1144.e1

17.

18. 19.

20. 23. 24. 25.

26. 27. 28.

29. 30. 31. 32.

word, subject heading word, unique identifier] [mp⫽ title, original title, abstract, name of substance word, subject heading word, unique identifier] saphenous vein/su, tr or femoral vein/su, tr or femoral artery/su, tr or popliteal artery/su, tr or inguinal canal/su, tr or exp leg/bs or/13-16 (angioplast* or catheteris* or catheriz* or transluminal* or percutaneous* or endovascular* or revascular* or stent* or blood vessel prosthesis/or blood vessel prosthesis implantation/or exercise therapy/or resistance training or walking*).mp. [mp⫽title, original title, abstract, name of substance word, subject heading word, unique identifier] 18 and (19 or 17) exp Venous Insufficiency/ec [Economics] exp Reoperation/ec [Economics] ((open or bypass or reconstruct*) adj3 (surger* or surgical* or repair*)).mp. [mp⫽title, original title, abstract, name of substance word, subject heading word, unique identifier] 18 and 25 restenosis/ec or treatment failure/ec or graft failure/or graft occlusion, vascular/ec ((clinical or cost) adj3 effective*).mp. [mp⫽title, original title, abstract, name of substance word, subject heading word, unique identifier] 3 or 6 or 7 or 8 or 23 or 24 or 27 or 28 or/9-12 (18 and 25) or 20 (29 or 30) and 31

Web of Science 1993-2009 This is a text word database, and does not use subject headings. # 8 423 #5 NOT #6 Refined by: Topic⫽(surgery OR surgical OR revascular* OR angioplast* OR stent* OR endovasc* OR bypass* OR prosthe* OR reoperat* OR reconstruct* OR repair* OR resteno* OR surgical* OR postoperative* OR operative* OR salvag* OR endolumin* or amput* OR treat* OR conservat* OR intervention* OR graft*) # 3 847 Topic⫽(“venous insufficien*” OR “vascular insufficien*” OR “arterial insufficien*” OR “peripheral occlusive” OR “peripheral vascular” OR “peripheral arterial” OR claudicat* OR ischaem* OR ischem* OR ulcer*) AND Topic⫽(leg* OR limb* OR femoral OR femoropopliteal OR “femoro-popliteal” OR infrainguinal OR inguinal OR “lower extremity” OR popliteal OR infrapopliteal) AND Topic⫽(cost OR costs OR saving* OR financ* OR money OR economic* OR reimburse* OR outcome* OR risk* OR “length of stay” OR “quality of life”) Refined by: Topic⫽(comparative* OR cohort* OR random* OR multicent* OR compare OR compari* OR rate OR survival OR disease free OR “disease free”) AND Languages⫽(ENGLISH).